Current methods for measuring optimal growth rates and subsequent efficient production of recombinant proteins in a bioreactor rely on indirect methods that are time consuming and can make the interpretation of observations error prone. This ultimately affects the reproducibility and the validity of bioreactor production in bio-pharma market, wasted research effort, time and expense. This Small Business Innovation Research Phase I project proposes to study the feasibility of developing unique label-free markers for cell cycle based on nuclear morphology correlated with refractive index variance. The measurements will use the Spatial Light Interference Microscopy (SLIM) technique developed at University of Illinois at Urbana Champaign. Once the feasibility is proven the work will continue for the development of a lab bench optical instrument for performing high-throughput label-free and cell cycle phase identification and scoring for bioreactor specimens using quantitative label-free assays of morphology and cell dynamics. The instrument will be commercialized into the research and bio-pharma market delivery of faster (100-fold higher throughput) and more accurate characterization of protein production in bioreactors.
Public Health Relevance Statement: Project Narrative Phi Optics proposes to develop an optical instrument for performing real time, quantitative high- throughput cell cycle classification and direct growth monitoring using label-free quantitative assays of morphology and dynamics. The instrument will allow novel bioreactor optimization strategies that could circumvent growth rate limitations and optimize feeding.
Project Terms: 3-Dimensional; Affect; Air; Algorithms; base; Biochemical; bioimaging; Biological; Biological Assay; Biophotonics; biophysical properties; Bioreactors; Businesses; Capital; Cell Cycle; Cell Cycle Progression; cell fixation; cell growth; Cell Line; Cell Proliferation; Cells; Classification; commercialization; Complex; Confusion; Consumption; density; design; Detection; Development; Disease; DNA; DNA Repair; Dyes; Enzymes; Exhibits; experimental study; Feasibility Studies; feeding; Fluorescence; Food production; Formulation; Funding; Goals; graphical user interface; Growth; Hour; Hyperplasia; Illinois; Image; Individual; Industry; Institutes; instrument; interest; Interference Microscopy; Interview; Investments; Label; Learning; Letters; Light; live cell imaging; Malignant Neoplasms; Measurement; Measures; Methods; Microscope; Microscopy; Monitor; Morphology; multimodality; nanometer; novel; Nuclear; Nucleic Acids; off-label use; optical imaging; Optical Instrument; Optics; Output; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population Growth; Price; Privatization; Procedures; Process; product development; Production; Productivity; programs; Proliferating Cell Nuclear Antigen; Proteins; prototype; Recombinant Proteins; Refractive Indices; Regulation; Reproducibility; Research; research and development; Resolution; response to injury; S Phase; Sales; Scanning; Scientist; Series; Small Business Innovation Research Grant; Specimen; Stains; statistics; Structure; Techniques; Technology; technology development; Testing; Texture; Thick; Time; Tissues; tomography; Universities; user-friendly; Validation; Vision; Work
